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Hajek, André, Benedikt Kretzler, and Hans-Helmut König. "Personality, Healthcare Use and Costs—A Systematic Review." Healthcare 8, no. 3 (September 9, 2020): 329. http://dx.doi.org/10.3390/healthcare8030329.
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Background: Thus far, there is a lack of a systematic review synthesizing empirical studies that analyze the link between personality factors and healthcare use (HCU) or costs. Consequently, the purpose of our systematic review is to give an overview of empirical findings from observational studies examining the association between personality factors and HCU or costs. Methods: PubMed, PsycINFO, and NHS EED (NHS Economic Evaluation Database) were searched. Observational studies examining the association between personality factors and HCU costs by using validated tools were included. Two reviewers performed study selection and data extraction and evaluated the study quality. Findings were synthesized qualitatively. Results: In total, n = 15 studies (HCU, n = 14; cost studies, n = 1) were included in the final synthesis. A few studies point to an association between conscientiousness and HCU (with mixed evidence). Some more evidence was found for an association between higher agreeableness, higher extraversion, and higher openness to experience and increased HCU. The majority of studies analyzed found a link between higher neuroticism and increased HCU. Conclusion: Personality factors, and particularly neuroticism, are associated with HCU. This knowledge is important to manage healthcare use. However, future research based on longitudinal data and studies investigating the link between personality characteristics and costs are required.
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Von den Hoff, Daan W., Floor A. C. Berden, Femke Atsma, Arnt F. A. Schellekens, and Joost P. H. Drenth. "Against All Odds? Addiction History Associated with Better Viral Hepatitis Care: A Dutch Nationwide Claims Data Study." Journal of Clinical Medicine 11, no. 4 (February 21, 2022): 1146. http://dx.doi.org/10.3390/jcm11041146.
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The elimination of viral hepatitis in target populations is crucial in reaching WHO viral hepatitis elimination goals. Several barriers for the treatment of viral hepatitis in people with addictive disorders have been identified, yet nationwide data on hepatitis healthcare utilization (HCU) in these patients are limited. We investigated whether a history of addictive disorder is associated with suboptimal hepatitis HCU, indicating failure to receive diagnostic care or treatment. We identified all newly referred viral hepatitis patients in the Netherlands between 2014 and 2019 by query of the Dutch national hospital claims database. Each patient’s first year of HBV or HCV care activities was collected and clustered in two categories, ‘optimal’ or ‘suboptimal’ hepatitis HCU. Optimal HCU includes antiviral therapy. We tested the association between addiction history and HCU, adjusted for sex, age, migrant status, and comorbidity. In secondary analyses, we explored additional factors affecting hepatitis HCU. We included 10,513 incident HBV and HCV patients, with 13% having an addiction history. Only 47% of all patients achieved optimal hepatitis HCU. Addiction history was associated with less suboptimal HCU (adjusted OR = 0.73, 95% CI = 0.64–0.82). Migration background was associated with suboptimal HCU (OR = 1.62, 95% CI = 1.50–1.76). This study shows that addiction history is associated with higher viral hepatitis HCU; thus, this population performs better compared to non-addicted patients. However, less than 50% of all patients received optimal hepatitis care. This study highlights the need to improve hepatitis HCU in all patients, with a focus on migrant populations. Linkage to care in the addicted patients is not studied here and may be a remaining obstacle to be studied and improved to reach WHO viral hepatitis elimination goals.
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Satwani, Prakash, Ruta Brazauskas, Staci D. Arnold, Naya He, Yimei Li, Richard Aplenc, Matt Hall, et al. "A Study of Predictors of Clinical Outcomes and Healthcare Utilization in Children with Sickle Cell Disease Undergoing Allogeneic Hematopoietic Cell Transplantation." Blood 126, no. 23 (December 3, 2015): 528. http://dx.doi.org/10.1182/blood.v126.23.528.528.
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Abstract Introduction: Current advances in allogeneic hematopoietic cell transplant (alloHCT) may warrant a paradigm shift in managing children with sickle cell disease (SCD). This study characterizes the clinical outcomes and health care utilization (HCU) of alloHCT for pediatric SCD. We hypothesize that early alloHCT will have improved clinical outcomes, and decreased HCU. Methods: The Center for International Blood and Marrow Transplant Research database was used to identify children 21 years or less with alloHCT for SCD in the United States. Patient data included comprehensive research forms (CRF) from 2000-13 and transplant essential data (TED) forms from 2000-11. CRFs provided clinical risk factors associated with overall survival, graft failure, grade III-IV acute GVHD, and GVHD related event free survival (GREFS) - the survival free of graft failure, chronic GVHD, or death. Risk factors included age, gender, performance status, year of alloHCT, prior SCD complications and therapy, CMV status, donor type, conditioning regimen, and GVHD prophylaxis. Due to low event rates and sample size, only univariate analysis of risk factors was performed. TED data was merged with Pediatric Health Information System (PHIS) inpatient data using a probabilistic merging algorithm to determine risk factors and clinical outcomes associated with HCU. Available PHIS adjusted cost data was used to determine the total adjusted cost for all inpatient admissions per patient per hospital day. To standardize these costs, the total adjusted cost per 30 hospital days was calculated for each patient and used as the primary HCU outcome. HCU outcomes were analyzed for the alloHCT year, day 0 to day +365. Results: CRF data for 161 patients showed an overall survival at 2 years of 90% (95% confidence intervals [CI] 85-95%): 96% (95% CI 89-100%) for related and unrelated cord blood transplant (CBT), 94% (95% CI 86-98%) matched siblings (MSD), and 74% (95% CI 54-90%) matched unrelated donors (MUD, p=0.002). All deaths occurred among children with pre-alloHCT complications of SCD, and deaths were due to organ failure (37.5%), infections (25%), GVHD (6.25%). Risk of death was significantly higher for children ≥10 years old (HR 21, p=0.003) and MUD compared to MSD (HR 5.88, p=0.005) but lower with cyclosporine A (CSA) GVHD prophylaxis versus FK506 (HR 0.33, p=0.031). 75% of deaths occurred before day +42. Cumulative acute GVHD incidence at day 100 was 14% (95% CI 9-20%)and was associated with age ≥10yrs (HR 2.63, p=0.035). Chronic GVHD incidence was 31% (95% CI 23-38%) at 2yrs, and factors associated were age ≥10yrs (HR 1.92, p=0.034), MUD vs MSD (HR 2.53, p=0.017), and CSA vs FK506 prophylaxis (HR 0.48, p=0.018). Chronic GVHD risk increased significantly after 2006 (HR 2.81, p=0.018). The 2yr GREFS was 64% (95% CI 56-71%). Age ≥10yrs (HR 2.2, p=0.005), MUD (vs MSD, HR 3.00, p=0.002) and CSA prophylaxis (vs FK506, HR 0.49, p=0.011) were significantly associated with this outcome. Among the 175 patients with combined TED and PHIS data, the median total adjusted cost was $117,393 per 30 hospital days per patient (range: $36,244-$515,640) during the alloHCT year with a median of 53 hospital days per patient (range: 16-304). Age ≥10yrs and HCU were not significantly associated (p=0.775). MSD had the lowest HCU compared to CBT and unrelated transplants (p<0.001). CBT and peripheral blood stem cells were associated with higher HCU compared to bone marrow (p=0.004). Increased HCU was associated with prior stroke (p=0.0004) and pain crises (p=0.0094) but not acute chest syndrome (p=0.2913). Overall SCD complication and severity indices correlated with increased HCU (p=0.052, p=0.0219, respectively). Conclusions: AlloHCT outcomes in children with SCD were linked to age and donor type suggesting that early alloHCT before age 10 years is preferred. Specifically, SCD severity and MUD alloHCT are associated with poorer outcomes and increased HCU. This supports the recommendation of early alloHCT, prior to onset of SCD complications, for children with SCD and an available MSD. Donor source and type had a significant impact on both outcomes and HCU. CBT outcomes were similar to MSD bone marrow; yet CBT had higher HCU suggesting additional analysis is needed to determine if the clinical benefit outweighs the cost. Further analysis is also needed to better understand and mitigate risk factors associated with poor outcomes and increased HCU following MUD alloHCT. Disclosures Arnold: Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program: Other: award. Hahn:NIH/NHLBI: Research Funding; Novartis: Equity Ownership.
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Newman, Lawrence, Pamela Vo, Lujia Zhou, Cristina Lopez Lopez, Andy Cheadle, Melvin Olson, and Juanzhi Fang. "Health Care Utilization and Costs in Patients With Migraine Who Have Failed Previous Preventive Treatments." Neurology: Clinical Practice 11, no. 3 (April 1, 2021): 206–15. http://dx.doi.org/10.1212/cpj.0000000000001076.
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ObjectiveTo characterize health care utilization (HCU) and associated costs among patients with migraine categorized by the number of preventive treatment failures (TFs; 1 TF, 2 TFs, and 3+ TFs) using real-world data.MethodsThis retrospective analysis identified adults with incident migraine diagnosis in the IBM MarketScan Commercial and Medicare Supplemental database between January 1, 2011, and June 30, 2015. TF was defined in the 2 years after the first migraine diagnosis period. One TF, 2 TFs, and 3+ TFs were defined as patients who had received only 2 preventive treatments (PTs), 3 PTs, and 4+ PTs in the 2-year period, respectively. A negative binomial model was used to analyze HCU data, and a 2-part model was used for cost data controlling for the preindex Deyo-Charlson Comorbidity Index.ResultsOverall, 24,282 patients with incident migraine who had failed at least 1 PT were included in the analysis. Of these, 72.7% (n = 17,653) had 1 TF, 20.2% (n = 4,900) had 2 TFs, and 7.1% (n = 1,729) had 3+ TFs. Adjusted annualized rates of all-cause and migraine-specific HCU increased with an increase in the number of TFs (1.4–4 times higher; all p < 0.0001 vs 1 TF). The mean total all-cause health care costs were higher by $3,732 (95% confidence interval [CI]: $2,708–$4,588) in patients with 2 TFs and by $8,912 (95% CI: $7,141–$10,822) in patients with 3+ TFs vs those with 1 TF. Outpatient costs were the key drivers of differences in health care costs.ConclusionsTF in patients with migraine was associated with a substantial resource and cost burden, which increased with the number of TFs.
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Takada, Yosuke, and Yasuhiro Otomo. "Study of Medical Supply and Demand Balance for the Nankai Trough Earthquake." Prehospital and Disaster Medicine 34, s1 (May 2019): s44. http://dx.doi.org/10.1017/s1049023x19001079.
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Introduction:The Nankai Trough, marking the boundary between the Eurasian Plate and the Philippine Sea Plate, is forecasted to create a tragic earthquake and tsunami within 30 years.Aim:To clarify the gap between medical supplies and demand.Methods:Collected the data of the estimation of injured persons from each prefecture throughout Japan, and also the number of Intensive Care Unit (ICU) and High Care Unit (HCU) beds in Japan from the Ministry of Health database. We re-calculated the number of severe cases based on official data. Moreover, we calculated the number of beds of hospitals with the capacity to receive severe patients.Results:The total number of disaster base hospitals is 723 hospitals with 6556 ICU beds, and 545 hospitals have 5,248 HCU beds throughout Japan. When the Nankai Trough earthquake occurs, 187 disaster base hospitals would be located in the area with seismic intensity 6-upper on the Japanese Seismic Intensity Scale of 0-7, and 79 disaster base hospitals would be located in the tsunami inundation area. The estimated total number of injured persons is 661,604 including 26,857 severe cases, 290,065 moderate cases, and 344,682 minor cases.Discussion:Even if all ICU and HCU beds are usable for severe patients, there will be 15,053 more beds needed. The Cabinet Office of Japan assumes that 60% of hospital beds would not be able to be used in an area of the seismic intensity of 6-upper. If 80% of beds are used in the non-disaster time, the number of beds which are usable at the time of a disaster will decrease more. The beds needed for severe patients would be significantly lacking when the Nankai Trough earthquake occurs. It will be necessary to start treatment of the severe patients who are “more likely to be saved more.”
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Ouattara, Eric, Amelie Bruandet, Aurélie Borde, Xavier Lenne, Florence Binder-Foucard, Maggie Le-bourhis-zaimi, Joris Muller, et al. "Risk factors of mortality among patients hospitalised with COVID-19 in a critical care or hospital care unit: analysis of the French national medicoadministrative database." BMJ Open Respiratory Research 8, no. 1 (October 2021): e001002. http://dx.doi.org/10.1136/bmjresp-2021-001002.
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ObjectiveTo explore mortality risk factors for patients hospitalised with COVID-19 in a critical care unit (CCU) or a hospital care unit (HCU).DesignRetrospective cohort analysis using the French national (Programme de médicalisation des systèmes d’information) database.SettingAny public or private hospital in France.Participants98 366 patients admitted with COVID-19 for more than 1 day during the first semester of 2020 were included. The underlying conditions were retrieved for all contiguous stays.Main outcome measuresIn-hospital mortality and associated risk factors were assessed using frailty Cox models.ResultsAmong the 98 366 patients included, 25 765 (26%) were admitted to a CCU. The median age was 66 (IQR: 55–76) years in CCUs and 74 (IQR: 57–85) years in HCUs. Age was the main risk factor of death in both CCUs and HCUs, with adjusted HRs (aHRs) in CCUs increasing from 1.60 (95% CI 1.35 to 1.88) for 46 to 65 years to 8.17 (95% CI 6.86 to 9.72) for ≥85 years. In HCUs, the aHR associated with age was more than two times higher. The gender was not significantly associated with death, aHR 1.03 (95% CI 0.98 to 1.09, p=0.2693) in CCUs. Most of the underlying chronic conditions were risk factors for death, including malignant neoplasm (CCU: 1.34 (95% CI 1.25 to 1.43); HCU: 1.41 (95% CI 1.35 to 1.47)), cirrhosis without transplant (1.41 (95% CI 1.22 to 1.64); 1.27 (95% CI 1.12 to 1.45)) and dementia (1.30 (95% CI 1.16 to 1.46); 1.07 (95% CI 1.03 to 1.12)).ConclusionThis analysis confirms the role of age as the major risk factor of death in patients with COVID-19 irrespective to admission to critical care and therefore supports the current vaccination policies targeting older individuals.
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Huang, Joanna C., Sudeep Karve, Sanchita Porwal, Kushan Thakkar, Thomas Marshall, and Tanja Rosenberg. "Health Care Utilization and Costs Among Patients with Chronic Myeloid Leukemia Using Tyrosine Kinase Inhibitors." Blood 132, Supplement 1 (November 29, 2018): 3537. http://dx.doi.org/10.1182/blood-2018-99-113809.
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Abstract INTRODUCTION: Tyrosine kinase inhibitors (TKIs) remain mainstay in the management of patients with CML. Several TKIs have been approved over the last two decades. Even though efficacy and safety remain as the primary drivers in treatment selection, in recent years importance has been placed on treatment affordability and economic burden associated with the long-term cancer treatments such as TKIs. However, current literature lacks real-world data on healthcare utilization (HCU) and costs among patients with CML using TKIs, which this study aims to address. METHODS: Retrospective cohort study was conducted using MarketScan Commercial, and Supplemental Medicare databases (2012-2016). Data includes medical and pharmacy utilization and costs for over 90 million individuals enrolled in employer-sponsored health-plans in the US. Data includes information on but not limited to medical diagnosis, procedures, drugs dispensed, date of service, health plan enrollment. Study involves adult patients (≥18 years) with ≥2 medical claims with a diagnosis of CML (ICD-9-CM: 205.10 - 205.12; ICD-10: C92.10-C92.12) and with a prescription claim for TKI. The date of first-TKI claim defined the index date. Patients were required to have continuous health plan enrollment ≥6 months before (defined as baseline period) and ≥6 months after index date. Selected patients were further classified into 5 sub-groups based on the index TKI observed (prescribed) post CML diagnosis (imatinib, dasatinib, nilotinib, bosutinib, ponatinib). Among the selected patients, all-cause HCU and costs were assessed from index date until end of database or end of enrollment, whichever occurred earlier. HCU and associated costs were assessed overall and by care settings including inpatient, emergency room, physician office, outpatient hospital, outpatient pharmacy, nursing facility and ancillary care. In addition, baseline (6 month) utilization and costs were assessed. Monthly and annual resource utilization and costs were reported for the overall CML cohort (across all TKI users) and by index TKI sub-groups. All costs were reported from a payer perspective (i.e., costs reimbursed by health plan) and adjusted to 2017 US dollars using the US consumer price index (medical component). All analyses were descriptive in nature. RESULTS: The study cohort included 2,213 CML patients. Distribution for the index TKI treatment was as follows: 41% imatinib, 36% dasatinib, 21% and 1% each for bosutinib and ponatinib. Mean age (standard deviation [SD]) of the cohort was 55 (15) years which was similar for individual TKI sub-groups. Majority of patients were males (55%) and 56% were enrolled in a preferred provider organization plan. The mean follow-up duration post-TKI initiation was 607 (442) days. The average baseline monthly all-cause costs were $4,365 with inpatient and pharmacy costs accounting for over 3/4th of the total costs (Figure 1). Post-TKI initiation the average monthly costs were twice ($9,288) compared with the baseline costs ($4,365) and the increase was primarily attributable to higher outpatient pharmacy costs ($6,619, accounted for 71% of total costs) (Figure 2). Monthly costs across other care settings (inpatient, outpatient, emergency room) were similar for the baseline and post-TKI initiation. On average patients had 1.4 office visits, 2.5 prescriptions and 0.7 hospital outpatient visits per month at baseline, which increased by 23%, 38% and 49%, respectively post TKI-initiation. During the 1st year post TKI-initiation, 17% patients in the overall CML cohort had at least 1 inpatient admission and this was consistent across individual TKI-sub-groups (except ponatinib, 50%). CONCLUSIONS: Findings on TKI utilization and costs in employer-sponsored health-plan database indicate that average costs and utilization were similar across the TKI sub-groups with pharmacy costs accounting for 71% of the total post TKI initiation costs. Overall, this study helps address the literature gap by providing recent real-world treatment care-setting specific utilization and costs among TKI uses and these data can be of value to several healthcare stakeholders including physicians, managed care plans and researchers in supporting clinical and formulary decisions and also serve as inputs for economic models. Finally, the sample sizes for ponatinib and bosutinb were small and results for these TKIs should be interpreted with caution. Disclosures Huang: ZS Associates: Employment; Novo Nordisk Inc: Equity Ownership; AstraZeneca: Research Funding. Karve:AbbVie: Employment, Equity Ownership. Porwal:ZS Associates: Employment. Thakkar:ZS Associates: Employment. Marshall:AbbVie: Employment, Equity Ownership. Rosenberg:AbbVie: Employment, Equity Ownership.
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Arnold, J. G., R. Srinivasan, T. S. Ramanarayanan, and M. DiLuzio. "Water resources of the Texas Gulf Basin." Water Science and Technology 39, no. 3 (February 1, 1999): 121–33. http://dx.doi.org/10.2166/wst.1999.0151.
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A geographic information system (GIS) has been integrated with a distributed parameter, continuous time, nonpoint source pollution model SWAT (Soil and Water Assessment Tool) for the management of water resources. This integration has proven to be effective and efficient for data collection and to visualize and analyze the input and output of simulation models. The SWAT-GIS system is being used to model the hydrology of eighteen major river systems in the United States (HUMUS). This paper focuses on the integration of SWAT (basin scale hydrologic model) with the Geographical Resources Analysis Support System (GRASS-GIS) and a relational database management system. The system is then applied to the Texas Gulf River basin. Input data layers (soils, land use, and elevation) were collected at a scale of 1:250,000 from various sources. Average monthly simulated and observed stream flow records from 1970-1979 are presented for the hydrologic cataloging units (HCU) defined by the United States Geological Survey (USGS) in the Texas Gulf basin. Average annual sediment yields computed from sediment rating curves are compared against simulated sediment yields from seven river basins within the Texas Gulf showing reasonable agreement.
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Sada, K. E., Y. Kojo, J. Fairburn-Beech, K. Sato, E. Hayashi, S. Akiyama, and M. Van-Dyke. "FRI0218 PREVALENCE, BURDEN OF DISEASE AND HEALTHCARE UTILIZATION AMONG PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) IN JAPAN 2005-2017." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 692.1–693. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1658.
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Background:EGPA is a rare vasculitis condition with very limited data available from real-world settings on burden and health care utilization (HCU), particularly in Japan.Objectives:To estimate the prevalence (overall and age, gender stratified) and describe HCU and treatment patterns among Japanese EGPA patients.Methods:This was a retrospective descriptive cohort study using a large administrative claims database covering up to more than 5 million corporate employees and their dependents (JMDC claim database) in Japan. Annual prevalence from 2005-2017 was estimated using two EGPA case definitions: a) patients with ≥1 ICD-10 code (2003 version) for EGPA (M30.1), b) patients with ≥2 ICD-10 codes for EGPA (M30.1) during the year in which prevalence was calculated. Among newly identified EGPA patients with no EGPA code in at least 12 months before, clinical burden, comorbidities, after hour visiting (AHV), all cause hospitalization, and treatment with drugs, including oral corticosteroid (OCS) use was described. OCS dose was expressed as prednisone equivalent.Results:The total number of newly identified patients in 2006-2016 was 45 persons and the mean (SD) age was 42.3 years (SD 14.7 years). The prevalence (per 1,000,000 patients) of EGPA with case definition a) in Japan in 2017 was estimated to be 38.0. The stratified prevalence (per 1,000,000) by age was: 2.3 in the group aged <18 years, 34.0 in those aged 18-50 years, and 91.1 in those aged ≥50 years, respectively. The prevalence in females (50.0) was approximately 1.7-fold higher than that in male (28.7). The prevalence, including stratified results, with definition b) was similar to that with definition a). In the newly identified patients, 60% of patients had at least one hospitalization and 55.6% had AHV, in the year after the first observed EGPA code during the study period. Following index date, new patients were treated: 77.8% with OCS, 11.1% with Azathioprine, 8.9% with intravenous immunoglobulin, 6.7% with Cyclophosphamide, 4.4% with Methotrexate, and 2.2% with Rituximab (non mutually exclusive). The mean (SD) maximum recorded daily dose of OCS in the 12 months follow up period was 53.5 (39.9) mg in new patients. The average dose (SD) of OCS in first month and last month in new patients was 39.1 (29.0) and 9.8 mg (4.8), respectively. Among those with at least a 14-day supply of OCS, 73.1% could be classified as adherent (≥80%) based on their 1-year proportion of days covered. 6.7% of EGPA patients experienced a potentially worsening with an increase of ≥10 mg daily OCS dose prescription following a previous prescription of <10mg.Conclusion:Analysis of the burden of disease and the use of medical resources in newly identified EGPA patients revealed that EGPA patients require hospitalizations and AHV, in addition to exposure to high doses of OCS. The appropriate medication for the treatment of EGPA to reduce burden on patients may need consider the pathophysiological state of EGPA patients.Disclosure of Interests:KEN-EI SADA Speakers bureau: I received speaker’s fee from GSK and Astra Zeneca K.K., Yoshiki Kojo Shareholder of: GSK, Employee of: GSK, Jolyon Fairburn-Beech Shareholder of: GSK, Employee of: GSK, Keiko Sato Shareholder of: GSK, Employee of: GSK, Etsuko Hayashi Shareholder of: GSK, Employee of: GSK, Shoko Akiyama Shareholder of: GSK, Employee of: GSK, melissa van-dyke Shareholder of: GSK, Employee of: GSK
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Gao, Yan, Yan Li, Ziyan Song, Zhenxing Jin, Xiao Li, and Chunluan Yuan. "Sortilin 1 Promotes Hepatocellular Carcinoma Cell Proliferation and Migration by Regulating Immune Cell Infiltration." Journal of Oncology 2022 (July 8, 2022): 1–13. http://dx.doi.org/10.1155/2022/6509028.
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Objectives. Recent evidence suggests that Sort1 promotes carcinogenesis and tumor progression in multiple types of cancers. This study investigates the role of Sort1 in hepatocellular carcinoma (HCC). Methods. The differentially expressed gene was screened through GEO and TCGA databases. The Sort1 gene was identified and its expression was then verified by TCGA and HCCDB (a database of hepatocellular carcinoma expression atlas) databases. The Human Protein Atlas database was used to assess the gene expression in tissues. The TCGA and KM-plotter databases were used to study the relationship between Sort1 and HCC. The correlation between Sort1 and immune cells was evaluated through the TIMER database. GO and KEGG enrichment analysis was used to investigate the possible mechanism. The role of Sort1 in cell proliferation and invasion of HCC was further explored through in vitro experiments. Result. The differentially expressed molecule obtained from database screening was Sort1. Its expression was higher in cancer tissues than in paracancerous ones, and it was mainly located in the cytoplasm. The TCGA, KM-plotter databases, and our study data showed that low expression of Sort1 in HCC patients had better overall survival (OS), progression-free survival (PFI), and disease-specific survival (DSS). Further analysis indicated a significant correlation between Sort1 expression and immune cell infiltration. The gene set enrichment analysis (GSEA) analysis showed that Sort1 affected the biological events of HCC by participating in the WNT, TGF-BETA, JAK, STAT, and CALCIUM signaling pathways. In vitro, cytological experiments demonstrated reduced expression of PCNA, Ki-67, Vimentin, N-cadherin, and MMP-9 mRNA after knocking down Sort1, although E-cadherin expression was promoted. Overall, these processes reduced the ability of proliferation and invasion of HCC cells. Conclusion. Downregulation of Sort1 can prolong the OS, PFI, and DSS of HCC patients. Furthermore, due to its link with immune cell infiltration, the Sort1 gene represents a potentially novel predictive biomarker of HCC. The growth of HCC can be significantly inhibited by interfering with Sort1; therefore, these results provide a potential target for developing anticancer strategies for HCC.
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Zeng, Lu, Xiude Fan, Xiaoyun Wang, Huan Deng, Kun Zhang, Xiaoge Zhang, Shan He, Na Li, Qunying Han, and Zhengwen Liu. "Bioinformatics Analysis based on Multiple Databases Identifies Hub Genes Associated with Hepatocellular Carcinoma." Current Genomics 20, no. 5 (December 3, 2019): 349–61. http://dx.doi.org/10.2174/1389202920666191011092410.
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Background: Hepatocellular carcinoma (HCC) is the most common liver cancer and the mechanisms of hepatocarcinogenesis remain elusive. Objective: This study aims to mine hub genes associated with HCC using multiple databases. Methods: Data sets GSE45267, GSE60502, GSE74656 were downloaded from GEO database. Differentially expressed genes (DEGs) between HCC and control in each set were identified by limma software. The GO term and KEGG pathway enrichment of the DEGs aggregated in the datasets (aggregated DEGs) were analyzed using DAVID and KOBAS 3.0 databases. Protein-protein interaction (PPI) network of the aggregated DEGs was constructed using STRING database. GSEA software was used to verify the biological process. Association between hub genes and HCC prognosis was analyzed using patients’ information from TCGA database by survminer R package. Results: From GSE45267, GSE60502 and GSE74656, 7583, 2349, and 553 DEGs were identified respectively. A total of 221 aggregated DEGs, which were mainly enriched in 109 GO terms and 29 KEGG pathways, were identified. Cell cycle phase, mitotic cell cycle, cell division, nuclear division and mitosis were the most significant GO terms. Metabolic pathways, cell cycle, chemical carcinogenesis, retinol metabolism and fatty acid degradation were the main KEGG pathways. Nine hub genes (TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK) were selected by PPI network and all of them were associated with prognosis of HCC patients. Conclusion: TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK were hub genes in HCC, which may be potential biomarkers of HCC and targets of HCC therapy.
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Yang, Wan-Xia, Yun-Yan Pan, and Chong-Ge You. "CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 May Be Potential Therapeutic Targets for Hepatocellular Carcinoma Using Integrated Bioinformatic Analysis." BioMed Research International 2019 (October 13, 2019): 1–16. http://dx.doi.org/10.1155/2019/1245072.
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Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality. The abnormal expression of genes is significantly related to the occurrence of HCC. The aim of this study was to explore the differentially expressed genes (DEGs) of HCC and to provide bioinformatics basis for the occurrence, prevention and treatment of HCC. The DEGs of HCC and normal tissues in GSE102079, GSE121248, GSE84402 and GSE60502 were obtained using R language. The GO function analysis and KEGG pathway enrichment analysis of DEGs were carried out using the DAVID database. Then, the protein–protein interaction (PPI) network was constructed using the STRING database. Hub genes were screened using Cytoscape software and verified using the GEPIA, UALCAN, and Oncomine database. We used HPA database to exhibit the differences in protein level of hub genes and used LinkedOmics to reveal the relationship between candidate genes and tumor clinical features. Finally, we obtained transcription factor (TF) of hub genes using NetworkAnalyst online tool. A total of 591 overlapping up-regulated genes were identified. These genes were related to cell cycle, DNA replication, pyrimidine metabolism, and p53 signaling pathway. Additionally, the GEPIA database showed that the CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 were associated with the poor survival of HCC patients. UALCAN, Oncomine, and HPA databases and qRT-PCR confirmed that these genes were highly expressed in HCC tissues. LinkedOmics database indicated these genes were correlated with overall survival, pathologic stage, pathology T stage, race, and the age of onset. TF analysis showed that MYBL2, KDM5B, MYC, SOX2, and E2F4 were regulators to these nine hub genes. Overexpression of CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 in tumor tissues predicted poor survival in HCC. They may be potential therapeutic targets for HCC.
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Jackson, Stewart, Scott Tyldesley, Barbara Baerg, and Ivo Olivotto. "Are the Creation and Maintenance of Databases in Healthcare Worthwhile? An Example of a Unique, Population-Based, Radiation Therapy Database." Healthcare Quarterly 15, no. 4 (October 29, 2012): 71–77. http://dx.doi.org/10.12927/hcq.2012.23195.
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Dai, Yaoyao, Sicheng Gao, Xing Liu, Qin Gao, Lan Zhang, Xingliang Fan, and Junfeng Zhu. "Effect of Aidi Injection plus TACE on Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials." Evidence-Based Complementary and Alternative Medicine 2018 (December 17, 2018): 1–10. http://dx.doi.org/10.1155/2018/9196409.
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We aim to conduct a meta-analysis of studies on the effect of Aidi injection combined with TACE in the treatment of hepatocellular carcinoma (HCC). China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Allied and Complementary Medicine Database (AMED), EMBASE, Web of Science, PubMed, and Cochrane Library databases to October 1, 2017, were searched to collect the studies. The data analysis was performed using RevMan 5.3 software. Totally 20 clinical trials with 774 (the experimental group: 447 cases; the control group: 327 cases) HCC patients were finally included in this meta-analysis. Meta-analysis results showed that Aidi injection combined with TACE can, to some extent, enhance the clinical effect and improve the overall survival. Meanwhile, it can increase HCC patients’ quality of life. Additionally, Aidi injection plus TACE can reduce adverse events including leukopenia, gastrointestinal reaction, and liver damage in HCC patients (all P < 0.05). Therefore, Aidi injection plus TACE may significantly enhance the clinical effect, suggesting that the combination of TCM and western medicine is promising. The exact outcome needs rigorously designed performances, multicenter, and large randomized controlled trials.
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Feng, Wei, and Shuo Han. "lncRNA ADAMTS9-AS1/circFN1 Competitively Binds to miR-206 to Elevate the Expression of ACTB, Thus Inducing Hypertrophic Cardiomyopathy." Oxidative Medicine and Cellular Longevity 2022 (March 31, 2022): 1–13. http://dx.doi.org/10.1155/2022/1450610.
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Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease and can result in substantial disability. The current study explored the potentials of long noncoding RNA- (lncRNA-) circular RNA- (circRNA-) microRNA- (miRNA-) messenger RNA (mRNA) networks in HCM. Firstly, HCM-related microarray data were procured from the GEO database, with differentially expressed genes (DEGs) obtained. HCM-related target genes were retrieved in combination with GeneCards and CTD databases, and candidate target genes were subsequently obtained by intersection screening. Further, an interaction network diagram of candidate target genes was constructed using the STRING database, and the hub genes in the network were determined according to the core degree. The “ClusterProfiler” package of the R software was adopted for GO and KEGG analyses of candidate target genes, to analyze the potential molecular pathways in HCM. Next, upstream miRNA, lncRNA, and circRNA of ACTB were predicted with RNAInter, mirDIP, TargetScan, DIANA-LncBase, and StarBase databases, followed by construction of lncRNA/circRNA-miRNA-mRNA coexpression networks. ACTB, miR-206, circFN1, and ADAMTS9-AS1 expression in peripheral blood samples from HCM patients and normal healthy controls were detected using RT-qPCR. Moreover, rat cardiomyocyte cell lines H9c2 and HEK293 cells were selected for in vitro verification of competitive endogenous RNA (ceRNA) regulation mechanism. A total of 15 candidate target genes related to HCM were screened using the online databases. Further protein-protein interaction analysis identified ACTB as the hub gene for HCM. The targeted binding relationship between miR-206, miR-145-5p, miR-1-3p, and ACTB was found. Furthermore, ADAMTS9-AS1 and circFN1 were discovered as the upstream genes of miR-206. Moreover, ADAMTS9-AS1, circFN1, and ACTB were found to be poorly expressed, and miR-206 was highly expressed in HCM. In vitro experimentation further confirmed that ADAMTS9-AS1 and circFN1 could competitively bind to miR-206, thereby augmenting ACTB expression. Taken all, ADAMTS9-AS1/circFN1-miR-206-ACTB regulatory network may involve in HCM occurrence, providing a novel theoretical basis for in-depth understanding of mechanism of HCM.
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Bai, Yun, Dan Lu, Di Qu, Yiwen Li, Ning Zhao, Guanghua Cui, Xue Li, et al. "The Role of ANGPTL Gene Family Members in Hepatocellular Carcinoma." Disease Markers 2022 (June 1, 2022): 1–14. http://dx.doi.org/10.1155/2022/1844352.
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Background. Hepatocellular carcinoma (HCC) is highly aggressive with a poor prognosis and survival rate. Certain ANGPTL members have been implicated in tumor progression. However, the relevance of the ANGPTL gene family to HCC remains poorly understood. In this study, we explored the role of ANGPTLs in the prognosis of HCC. Methods. From the CCLE database, we studied the expression of ANGPTLs in a range of cancer cell lines. The UCSC, HCCDB, and Human Protein Atlas databases were used to analyze the differences in mRNA and protein expression of ANGPTLs in HCC tissues. Additionally, the correlation between ANGPTL mRNA and methylation levels and clinicopathological features were assessed in the TCGA database. The correlation between ANGPTL mRNA and overall survival was determined by the Kaplan-Meier plotter. cBioPortal database was used to analyze ANGPTL genomic alterations. Genes associated with ANGPTLs were determined by enrichment with KEGG. Moreover, the differentially expressed genes of ANGPTLs were analyzed by the LinkedOmics database, and the KEGG pathway and miRNA targets of ANGPTLs were also enriched. Results. There was a significant correlation between the ANGPTL members (excluding ANGPTL2) and the prognosis of HCC patients according to the Kaplan-Meier plotter analysis ( p < 0.05 ). ANGPTL1 was the gene with the highest mutation frequency. ANGPTLs are involved in certain pathways that may influence the development of HCC. Conclusion. In summary, the expression of some members of ANGPTLs was significantly correlated with HCC prognosis, suggesting that the ANGPTL gene family members may be promising molecular markers for HCC treatment and prognosis.
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Wang, Qian, Yan Liang, Can Peng, and Peng Jiang. "Network Pharmacology-Based Study on the Mechanism of Scutellariae Radix for Hepatocellular Carcinoma Treatment." Evidence-Based Complementary and Alternative Medicine 2020 (October 26, 2020): 1–12. http://dx.doi.org/10.1155/2020/8897918.
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Hepatocellular carcinoma (HCC) is a malignant tumor without effective therapeutic drugs for most patients in advanced stages. Scutellariae Radix (SR) is a well-known anti-inflammatory and anticarcinogenic herbal medicine. However, the mechanism of SR against HCC remains to be clarified. In the present study, network pharmacology was utilized to characterize the mechanism of SR on HCC. The active components of SR and their targets were collected from the traditional Chinese medicine systems pharmacology database and the traditional Chinese medicine integrated database. HCC-related targets were acquired from the liver cancer databases OncoDB.HCC and Liverome. The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. Component-component target and protein-protein interaction networks were set up. A total of 143 components of SR were identified, and 37 of them were considered as candidate active components. Fifty targets corresponding to 29 components of SR were mapped with targets of HCC. Functional enrichment analysis indicated that SR exerted an antihepatocarcinoma effect by regulating pathways in cancer, hepatitis B, viral carcinogenesis, and PI3K-Akt signaling. The holistic approach of network pharmacology can provide novel insights into the mechanistic study and therapeutic drug development of SR for HCC treatment.
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Gheidarloo, Mahshid, Roya Kelishadi, Silva Hovsepian, Mojtaba Keikha, and Mahin Hashemipour. "The association between prenatal exposure to organochlorine compounds and neonatal thyroid hormone levels: a systematic review." Journal of Pediatric Endocrinology and Metabolism 33, no. 1 (January 28, 2020): 21–33. http://dx.doi.org/10.1515/jpem-2019-0336.
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AbstractIn this systematic review, the association between prenatal exposure to organochlorine pesticides (OCPs) and neonatal thyroid hormone levels was studied. A systematic search of scientific literature was performed from the PubMed, SCOPUS and ISI web of science electronic bibliographic databases. The search strategy for the review was [(organochlorine OR “organochlorine pesticides” OR “organochlorine pollutants” OR “organochlorine pollutant”) AND (“thyroid hormone” OR triiodothyronine OR Thyroxine OR “fetal thyroid function” OR “thyroid function” OR “Thyroid Stimulating Hormone” AND “prenatal” AND “maternal exposure”)] in English sources. In this review, 305 papers (PubMed: 30; Scopus: 29; ISI: 246) were identified through an electronic database search. Twenty-seven articles were assessed for eligibility, from which 16 qualified articles were selected for the final evaluation. The most common OCP metabolites which were evaluated in order were hexachlorobenzene (HCB) (13 studies), pp-dichlorodiphenyldichloroethylene (pp-DDE) (13 studies), hexachlorocyclohexane (HCH) (10 studies) and dichlorodiphenyltrichlorethane (DDT) (eight studies). A review of the documents related to the association of prenatal exposure of OCPs with fetal or neonatal thyroid function tests provides us with heterogeneous data in this field. Factors such as differences in the studied populations and their area, ethnic and genetic background, time and rate of exposure, possible interaction of other thyroid-disrupting environmental factors and dietary intake of micronutrients such as iodine and/or selenium are considered the main limitations for making an accurate conclusion. For some OCPs including DDT, DDE, HCH and HCB, there are supporting evidences, and it is suggested that their exposure could potentially alter the fetal thyroid function and consequently impair the neurodevelopment process of the infants.
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Liu, Shuqing, Lei Jia, Bing Quan, Guang Rong, Min Li, Ronggen Xie, Yanling Cai, Yuzhen Bi, and Siyuan Han. "Coiled-Coil Domain-Containing Protein 45 Is a Potential Prognostic Biomarker and Is Associated with Immune Cell Enrichment of Hepatocellular Carcinoma." Disease Markers 2022 (December 29, 2022): 1–22. http://dx.doi.org/10.1155/2022/7745315.
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Objective. The role of coiled-coil domain-containing protein 45 (CCDC45) in the development of hepatocellular carcinoma (HCC) has not been reported. The present study is aimed at investigating the expression and prognosis of CCDC45 in HCC and its relevance to immune infiltration. Methods. We conducted CCDC45 expression analysis using The Cancer Genome Atlas (TCGA) tumor database, the Human Protein Atlas (HPA) database, and the Tumor Immunological Evaluation Resource (TIMER). We used the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) database to show the correlation of CCDC45 with clinical features. We examined the prognostic impact of CCDC45 expression levels on HCC patients with the Kaplan-Meier mapper database. Genes coexpressed with CCDC45 and its regulators were also identified using LinkedOmics. The enriched Gene Ontology (GO) categories and associated signaling pathways were estimated using GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Assay (GSEA) pathway data. Correlations between CCDC45 and cancer immune infiltration was analyzed through the TIMER and an integrated repository portal for Tumor-Immune System Interactions (TISIDB) databases. Results. The expression of CCDC45 was elevated in HCC tissues compared to adjacent liver tissues, and overexpression of CCDC45 was significantly correlated with tumor stage. Furthermore, HCC patients with CCDC45 overexpression had a shorter overall survival (OS). Functional network analysis indicated that CCDC45 was involved in homologous recombination, spliceosome, and DNA replication. Interestingly, CCDC45 expression was positively correlated with the level of immune cell infiltration. Conclusions. CCDC45 is associated with prognosis and immune infiltration of HCC and may be a potential therapeutic target for HCC.
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Wang, Shiying, Liping Zhuang, and Zhiqiang Meng. "Hepatocellular Carcinoma More Than 3 cm in Diameter: A Systematic Review of Transcatheter Arterial Chemoembolization Plus Percutaneous Ethanol Injection versus Transcatheter Arterial Chemoembolization Alone." ISRN Gastroenterology 2013 (June 27, 2013): 1–9. http://dx.doi.org/10.1155/2013/526024.
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Objective. To identify the efficiency and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol (PEI) for patients with hepatocellular carcinoma (HCC) more than 3 cm in diameter in comparison with those of transcatheter arterial chemoembolization monotherapy. Methods. All databases were searched up to February 22, 2013. The literature retrieval was conducted through Pubmed, Web of Science, and Cochrane Library. We also searched Chinese databases, including Chinese National Knowledge Infrastructure (CNKI), Chinese Biology Medicine (CBM), Wanfang database, and VIP Database for Chinese Technical Periodicals without language limitations. Results. Based on the criteria, we found 12 RCTs including 825 patients. Our results showed that TACE combined with PEI therapy compared with TACE monotherapy improved overall survival and tumor response. Conclusion. The combination of TACE and PEI compared with TACE monotherapy improved overall survival rates and tumor response of patients with large HCC. Besides, larger and more methodologically rigorous clinical trials are needed to confirm this outcome.
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Ju, Gaoda, Tianhao Zhou, Rui Zhang, Xiaozao Pan, Bing Xue, and Sen Miao. "DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma." PeerJ 9 (August 3, 2021): e11929. http://dx.doi.org/10.7717/peerj.11929.
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Background Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. Methods We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. Results DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). Conclusion These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.
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Chen, Miao, Duo Wang, Junjie Liu, Zhizhan Zhou, Zhanling Ding, Lianfeng Liu, Danke Su, and Hang Li. "MicroRNA-587 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting Ribosomal Protein SA." BioMed Research International 2020 (September 7, 2020): 1–12. http://dx.doi.org/10.1155/2020/3280530.
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Background. Hepatocellular carcinoma (HCC) is one of the most highly aggressive cancer worldwide with an extremely poor prognosis. Evidence has revealed that microRNA-587 (miR-587) is abnormally expressed in a series of cancers. However, its expressions and functions in HCC have not been clearly acknowledged. Methods. We detected the expression level of miR-587 both in the Gene Expression Omnibus (GEO) database and 86 paired clinical HCC tissues together with paired adjacent normal tissues by quantitative real-time PCR (qRT-PCR). Afterwards, the transfected HCC cell line SMMC-7721 cells were collected for the cell proliferation assay, cell-cycle arrest, cell migration, and invasion assays to explore the roles of miR-587 in regulating cellular function. In addition, bioinformatics analysis, combined with qRT-PCR and dual-luciferase reporter assays, were performed to confirm whether ribosomal protein SA (RPSA) mRNA was the direct target gene of miR-587. Moreover, the Cancer Genome Atlas (TCGA) and GEO databases as well as 86 paired clinical HCC tissues were used to verify the negative regulation between miR-587 and RPSA. Results. In the present study, both the GEO database (GSE36915 and GSE74618) analysis and qRT-PCR analysis of 86 paired clinical tissues showed that miR-587 was significantly downregulated in HCC tissues. The overexpression of miR-587 inhibited proliferation, cell cycle, migration, and invasion in SMMC-7721 cells. In addition, miR-587 directly interacted with the 3′-untranslated region (UTR) of RPSA. Moreover, miR-587 overexpression directly suppressed RPSA expression, and the two genes were inversely expressed in HCC based on the analyses in TCGA and GEO (GSE36376) databases and qPCR analysis of 86 paired clinical tissues. Conclusion. Our results demonstrate that miR-587 is downexpressed in HCC and regulates the cellular function by targeting RPSA.
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Keller, Jesse W., Maria Majella Doyle, Andrea Wang-Gillam, Elizabeth Brunt, Neeta Vachhajarani, William Chapman, and Benjamin R. Tan. "Analysis of the genomic profile of biphenotypic tumors compared to cholangiocarcinoma and hepatocellular carcinoma." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 226. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.226.
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226 Background: Biphenotypic (combined HCC/Cholangiocarcinoma) tumors represent a minority of primary liver cancers. While databases such as the Catalog of Somatic Mutations in Cancer (COSMIC) have genetic information on a large number of cases of HCC and Cholangiocarcinoma, there is little known about rarer Biphenotypic tumors. In this analysis we examine the results of targeted next-generation sequencing to assess genomic differences between these tumors. We utilize the COSMIC database for comparison. Methods: The database of theIRB-approved Washington University Hepatobiliary Registry identified patients with HCC, cholangiocarcinoma and biphenotypic tumors with specimens evaluated utilizing next generation sequencing via a Comprehensive Cancer Gene Set. Further data on corresponding genes was collected from the COSMIC database (v66) for comparison. Results: In this descriptive analysis 15 patients with biphenotypic tumors, 7 patients with HCC and 6 patients with cholangiocarcinoma are presented. The percent of samples with corresponding genetic mutations are outlined (table). These are compared to existing COSMIC data. Conclusions: Biphenotypic tumors had high levels of mutations in EGFR, P53 and Flt3. Mutations in MET, BRAF, CSF1, and MAPK1 were largely isolated to biphenotypic tumors. Mutations in CTNBB1 were isolated to cases of HCC. Notably, mutations in EGFR, Flt3 and FGFR4 were found in all three tumors in higher numbers than seen via review of COSMIC data. Overall, Biphenotypic tumors are genetically complex tumors that share many features of HCC and cholangiocarcinoma. [Table: see text]
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SAGHEER, ALAA, NAOYUKI TSURUTA, RIN-ICHIRO TANIGUCHI, and SAKASHI MAEDA. "APPEARANCE FEATURE EXTRACTION VERSUS IMAGE TRANSFORM-BASED APPROACH FOR VISUAL SPEECH RECOGNITION." International Journal of Computational Intelligence and Applications 06, no. 01 (March 2006): 101–22. http://dx.doi.org/10.1142/s1469026806001800.
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In this paper we propose a new appearance based system which consists of two stages: visual speech feature extraction and classification, followed by recognition of the extracted feature, thereby the result is a complete lip-reading system. This lip-reading system employs our Hyper Column Model (HCM) approach to extract and classify the visual features and uses the Hidden Markov Model (HMM) for recognition. This paper addresses mainly the first stage; i.e. feature extraction and classification. We investigate the HCM performance to achieve feature extraction and classification and then compare the performance when replacing HCM with Fast Discrete Cosine Transform (FDCT). Unlike FDCT, HCM could extract the entire features without any loss. Also the experiments have shown that HCM is generally better than FDCT and provides a good distribution of the phonemes in the feature space for recognition purposes. For fair comparison, two databases are exploited with three different sets of resolution for each database. One of these two databases is designed to include shifted and scaled objects. Experiments reveal that HCM is capable of recovering and dealing with such image restrictions whereas the effectiveness of FDCT drops drastically especially for new subjects.
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Siddiqui, Mohammad Faridul Haque, Parashar Dhakal, Xiaoli Yang, and Ahmad Y. Javaid. "A Survey on Databases for Multimodal Emotion Recognition and an Introduction to the VIRI (Visible and InfraRed Image) Database." Multimodal Technologies and Interaction 6, no. 6 (June 17, 2022): 47. http://dx.doi.org/10.3390/mti6060047.
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Multimodal human–computer interaction (HCI) systems pledge a more human–human-like interaction between machines and humans. Their prowess in emanating an unambiguous information exchange between the two makes these systems more reliable, efficient, less error prone, and capable of solving complex tasks. Emotion recognition is a realm of HCI that follows multimodality to achieve accurate and natural results. The prodigious use of affective identification in e-learning, marketing, security, health sciences, etc., has increased demand for high-precision emotion recognition systems. Machine learning (ML) is getting its feet wet to ameliorate the process by tweaking the architectures or wielding high-quality databases (DB). This paper presents a survey of such DBs that are being used to develop multimodal emotion recognition (MER) systems. The survey illustrates the DBs that contain multi-channel data, such as facial expressions, speech, physiological signals, body movements, gestures, and lexical features. Few unimodal DBs are also discussed that work in conjunction with other DBs for affect recognition. Further, VIRI, a new DB of visible and infrared (IR) images of subjects expressing five emotions in an uncontrolled, real-world environment, is presented. A rationale for the superiority of the presented corpus over the existing ones is instituted.
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Luo, Guanshui, Jianguo Xu, Zhenglin Xia, Shuai Liu, Hong Liu, Ke He, and Guoan Xiang. "SSRP1 Is a Prognostic Biomarker Correlated with CD8+ T Cell Infiltration in Hepatocellular Carcinoma (HCC)." BioMed Research International 2021 (February 23, 2021): 1–10. http://dx.doi.org/10.1155/2021/9409836.
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Background. Hepatocellular carcinoma (HCC), one of the most common primary malignancies, is theoretically an epitope candidate for immune checkpoint inhibitors, and therefore, the identification of HCC biomarkers is important. Structure-specific recognition protein 1 (SSRP1) is involved in almost all chromatin-related processes, including DNA replication, repair, and transcription. However, its role in HCC remains to be elucidated. Methods. This study investigated the expression of SSRP1 in HCCDB, Oncomine, HPA, and other databases. The prognostic value of SSRP1 in HCC and its relationship with clinical characteristics were then explored using Kaplan-Meier plotter. At the same time, SSRP1 coexpression genes were explored and functionally annotated in the LinkedOmics database. Finally, the correlation between the SSRP1 expression and HCC immune cell infiltration was explored in TIMER and online single-cell sequencing database. Results. Significantly elevated transcriptional and proteomic SSRP1 expressions were found in HCC. Increased SSRP1 mRNA expression was significantly correlated with relevant clinicopathological parameters such as immune cells. Notably, the SSRP1 expression was positively correlated with the infiltration levels of Treg and CD8+ T cells, especially exhausted CD8+ T cells. Interestingly, the SSRP1 expression was higher in both tumor Treg and exhausted CD8+ T cells than in adjacent tissues. Conclusion. SSRP1, as a new prognostic marker for HCC, promotes HCC development by influencing the infiltration of depleted CD8+ T cells and may influence the effect of immunotherapy.
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Liu, Xuxu, Yuanhang He, Pengfei Wang, Jie Hu, Chenjun Hao, Qiang Wang, Yang Yang, et al. "ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma." Disease Markers 2022 (March 3, 2022): 1–25. http://dx.doi.org/10.1155/2022/5791471.
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Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.
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Wu, Qing, Yangzhi Hu, Qinghui Ma, Shanglin Yang, Junpeng Chen, Shunqian Wen, and Guanqun Liao. "Comprehensive Analysis of RAPGEF2 for Predicting Prognosis and Immunotherapy Response in Patients with Hepatocellular Carcinoma." Journal of Oncology 2022 (April 26, 2022): 1–11. http://dx.doi.org/10.1155/2022/6560154.
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Background. Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide. Additionally, deletion of RAPGEF2 plays a critical role in CNV and related to tumor immune microenvironment, whereas the prognostic potential of RAPGEF2 in HCC patient needs to be explored. Methods. We looked for prognostic potential genes in HCC using a variety of R programs. Then, using the LASSO Cox regression, we thoroughly evaluated and integrated the RAPGEF2-related genes from TCGA database. Meanwhile, utilizing TCGA and ICGA databases, the link between RAPGEF2 and immunotherapy response in HCC was studied. In vivo, the effect of RAPGEF2 on tumor development and the capacity of natural killer (NK) cells to recruit were confirmed. To ascertain the connection between RAPGEF2-related genes and the prognosis of HCC, a prognostic model was created and validated. Result. We demonstrated RAPGEF2 has a differential expression, and patients with deletion of RAPGEF2 gene get shorter survival in HCC. Additionally, the tissues without RAPGEF2 have a weaker ability to recruit the NK cells and response to immunotherapy. After that, we scoured the database for eight RAPGEF2-related genes linked with a better prognosis in HCC patients. Additionally, silencing RAPGEF2 accelerated tumor development in the HCC mouse model and decreased CD56+ NK cell recruitment in HCC tissues. TCGA database was used to classify patients into low- and high-risk categories based on the expression of related genes. Patients in the low-risk group had a significantly greater overall survival than those in the high-risk group ( P < 0.001 ). Meanwhile, the low-risk group demonstrated connections with the NK cell and immunotherapy response. Finally, the prognostic nomogram showed a high sensitivity and specificity for predicting the survival of HCC patients at 1, 2, and 3 years. Conclusion. The prognostic model based on RAPGEF2 and RAPGEF2-related genes showed an excellent predictive performance in terms of prognosis and immunotherapy response in HCC, therefore establishing a unique prognostic model for clinical assessment of HCC patients.
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Wu, Qing, Yangzhi Hu, Qinghui Ma, Shanglin Yang, Junpeng Chen, Shunqian Wen, and Guanqun Liao. "Comprehensive Analysis of RAPGEF2 for Predicting Prognosis and Immunotherapy Response in Patients with Hepatocellular Carcinoma." Journal of Oncology 2022 (April 26, 2022): 1–11. http://dx.doi.org/10.1155/2022/6560154.
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Background. Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide. Additionally, deletion of RAPGEF2 plays a critical role in CNV and related to tumor immune microenvironment, whereas the prognostic potential of RAPGEF2 in HCC patient needs to be explored. Methods. We looked for prognostic potential genes in HCC using a variety of R programs. Then, using the LASSO Cox regression, we thoroughly evaluated and integrated the RAPGEF2-related genes from TCGA database. Meanwhile, utilizing TCGA and ICGA databases, the link between RAPGEF2 and immunotherapy response in HCC was studied. In vivo, the effect of RAPGEF2 on tumor development and the capacity of natural killer (NK) cells to recruit were confirmed. To ascertain the connection between RAPGEF2-related genes and the prognosis of HCC, a prognostic model was created and validated. Result. We demonstrated RAPGEF2 has a differential expression, and patients with deletion of RAPGEF2 gene get shorter survival in HCC. Additionally, the tissues without RAPGEF2 have a weaker ability to recruit the NK cells and response to immunotherapy. After that, we scoured the database for eight RAPGEF2-related genes linked with a better prognosis in HCC patients. Additionally, silencing RAPGEF2 accelerated tumor development in the HCC mouse model and decreased CD56+ NK cell recruitment in HCC tissues. TCGA database was used to classify patients into low- and high-risk categories based on the expression of related genes. Patients in the low-risk group had a significantly greater overall survival than those in the high-risk group ( P < 0.001 ). Meanwhile, the low-risk group demonstrated connections with the NK cell and immunotherapy response. Finally, the prognostic nomogram showed a high sensitivity and specificity for predicting the survival of HCC patients at 1, 2, and 3 years. Conclusion. The prognostic model based on RAPGEF2 and RAPGEF2-related genes showed an excellent predictive performance in terms of prognosis and immunotherapy response in HCC, therefore establishing a unique prognostic model for clinical assessment of HCC patients.
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Li, Chuanfei, Feng Qin, Hao Hong, Hui Tang, Xiaoling Jiang, Shuangyan Yang, Zhechuan Mei, and Di Zhou. "Identification of Flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis." PeerJ 7 (September 6, 2019): e7619. http://dx.doi.org/10.7717/peerj.7619.
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Hepatocellular carcinoma (HCC) is a common yet deadly form of malignant cancer. However, the specific mechanisms involved in HCC diagnosis have not yet fully elucidated. Herein, we screened four publically available Gene Expression Omnibus (GEO) expression profiles (GSE14520, GSE29721, GSE45267 and GSE60502), and used them to identify 409 differentially expressed genes (DEGs), including 142 and 267 up- and down-regulated genes, respectively. The DAVID database was used to look for functionally enriched pathways among DEGs, and the STRING database and Cytoscape platform were used to generate a protein-protein interaction (PPI) network for these DEGs. The cytoHubba plug-in was utilized to detect 185 hub genes, and three key clustering modules were constructed with the MCODE plug-in. Gene functional enrichment analyses of these three key clustering modules were further performed, and nine core genes including BIRC5, DLGAP5, DTL, FEN1, KIAA0101, KIF4A, MCM2, MKI67, and RFC4, were identified in the most critical cluster. Subsequently, the hierarchical clustering and expression of core genes in TCGA liver cancer tissues were analyzed using the UCSC Cancer Genomics Browser, and whether elevated core gene expression was linked to a poor prognosis in HCC patients was assessed using the GEPIA database. The PPI of the nine core genes revealed an interaction between FEN1, MCM2, RFC4, and BIRC5. Furthermore, the expression of FEN1 was positively correlated with that of three other core genes in TCGA liver cancer tissues. FEN1 expression in HCC and other tumor types was assessed with the FIREBROWSE and ONCOMINE databases, and results were verified in HCC samples and hepatoma cells. FEN1 levels were also positively correlated with tumor size, distant metastasis and vascular invasion. In conclusion, we identified nine core genes associated with HCC development, offering novel insight into HCC progression. In particular, the aberrantly elevated FEN1 may represent a potential biomarker for HCC diagnosis and treatment.
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Rudnev, Sergey G., Olga A. Starunova, Elena Z. Godina, Alla E. Ivanova, Alexander V. Zubko, and Vladimir I. Starodubov. "The Russian bioimpedance database: an update." Journal of Electrical Bioimpedance 13, no. 1 (January 1, 2022): 66–72. http://dx.doi.org/10.2478/joeb-2022-0010.
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Abstract Extensive bioelectrical impedance analysis (BIA) data have the potential of health monitoring and the assessment of health risks at the population level. The importance of BIA data lies in their availability and abundance for many countries. In Russia, mass BIA data are generated by the national network of health centers (HCs). Our aim was to describe the structure and capabilities of the updated HCs’ BIA database. Upon several requests between 2012 and 2020, 369 HCs representing all Federal districts of Russia and 60 out of 85 Federal subjects in them, submitted raw bioimpedance data which were obtained using the same type of BIA instrument, namely ABC-01 ‘Medas’ (SRC Medas, Russia). After application of strict selection criteria, 2,429,977 BIA measurement records were selected that formed the updated 2010-2019 HCs’ database. Various slices of the BIA data are described according to spatiotemporal, demographic and other characteristics. Reference curves of the bioimpedance phase angle according to age and sex are presented. Limitations and prospects for further work are outlined. We believe that, after appropriate sampling, the database can be utilized to study biological, geographical, social and other associations of the bioimpedance and body composition parameters, for generating updated national references, international comparisons and data standardization.
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Zhang, Di, Liping Ye, Shuang Hu, Qingqing Zhu, Chenxi Li, and Chengming Zhu. "Comprehensive Analysis of the Expression and Prognostic Value of LMAN2 in HER2+ Breast Cancer." Journal of Immunology Research 2022 (June 6, 2022): 1–26. http://dx.doi.org/10.1155/2022/7623654.
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Lectin, Mannose Binding 2 (LMAN2) encodes a type I transmembrane lectin that shuttles between the plasma membrane, the Golgi apparatus, and the endoplasmic reticulum. However, its expression, prognosis, and function in invasive breast carcinoma remain unknown. Nine databases were consulted to evaluate LMAN2 expression and prognosis in breast cancer. The possible function of LMAN2 in breast cancer was investigated in the Human Cell Landscape (HCL) database, Gene Regulatory Network database (GRNdb), and CancerSEA database. Moreover, N6-methyladenosine (m6A) modifications were analyzed using the RMBase v2.0 and M6A2Target databases. Seven databases were then used to analyze the potential action mechanisms of LMAN2. Our findings suggest that LMAN2, which is expressed at a high level in breast cancer, is linked to an unfavorable prognosis. Therefore, LMAN2 has the potential to be utilized as a treatment target in breast cancer. Furthermore, the single-cell analysis illustrated that LMAN2 expression had a positive link to breast cancer stemness, proliferation, metastasis, and differentiation. Moreover, m6A modifications were found in the LMAN2 gene. Consequently, modifications to m6A methylation may influence LMAN2 expression, which is associated with the homologous recombination (HR) in its DNA damage repair pathway .
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Huang, Xufeng, Hafiz Muzzammel Rehman, Attila Gábor Szöllősi, and Shujing Zhou. "Network Pharmacology-Based Approach Combined with Bioinformatic Analytics to Elucidate the Potential of Curcumol against Hepatocellular Carcinoma." Genes 13, no. 4 (April 7, 2022): 653. http://dx.doi.org/10.3390/genes13040653.
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Purpose: Modern, open-source databases provide an unprecedented wealth of information to help drug development. By combining data available in these databases with the proper bioinformatical tools, we can elucidate the molecular targets of natural compounds. One such molecule is curcumol, a guaiane-type sesquiterpenoid hemiketal isolated from Rhizoma Curcumae, which is used for a broad range of diseases in traditional Chinese and Indian medicine. It has been reported to exert anti-tumor activity, but the intrinsic molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, the present study was designed to reveal the predictive targets and biological mechanisms of curcumol against HCC via a network pharmacology-based approach combined with bioinformatic analytics and to provide proof of concept for further similar investigations. Methods: Data available from open-source databases (Traditional Chinese Medicine Systems Pharmacology, Comparative Toxicogenomic Database, The Cancer Genome Atlas, the Human Protein Atlas project) was processed with the help of a variety of open-source tools (SwissADME, SwissTargetPrediction, JVenn, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GeneMANIA, Cytoscape). Results: In the present study, the potential of curcumol against HCC was unraveled by network pharmacology-based elucidation. It suggests that curcumol shows exciting druggability with 44 potent homo sapiens biotargets against HCC. The GO terms and KEGG pathways enrichment analyses, curcumol-targets-pathways-HCC network, PPI network, and corresponding in-depth topological analyses, as well as survival analysis, molecular docking simulation indicate that the potential mechanism of curcumol against HCC is complicated, as it may act in various ways, mainly by inducing apoptosis and modulating the inflammatory response, increasing presentation of HCC-specific protein. Conclusion: The present study highlights the potential of curcumol against HCC, giving reference to further experimental study. It also presents a roadmap that can be followed to conduct in silico prescreening of other compounds of interest.
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Gao, Shan, Dongjie Zhu, Jian Zhu, Lianqiang Shen, Ming Zhu, and Xuefeng Ren. "Screening Hub Genes of Hepatocellular Carcinoma Based on Public Databases." Computational and Mathematical Methods in Medicine 2021 (October 26, 2021): 1–15. http://dx.doi.org/10.1155/2021/7029130.
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Tumor recurrence and metastasis often occur in HCC patients after surgery, and the prognosis is not optimistic. Hence, searching effective biomarkers for prognosis of is of great importance. Firstly, HCC-related data was acquired from the TCGA and GEO databases. Based on GEO data, 256 differentially expressed genes (DEGs) were obtained firstly. Subsequently, to clarify function of DEGs, clusterProfiler package was used to conduct functional enrichment analyses on DEGs. Protein-protein interaction (PPI) network analysis screened 20 key genes. The key genes were filtered via GEPIA database, by which 11 hub genes (F9, CYP3A4, ASPM, AURKA, CDC20, CDCA5, NCAP, PRC1, PTTG1, TOP2A, and KIFC1) were screened out. Then, univariate Cox analysis was applied to construct a prognostic model, followed by a prediction performance validation. With the risk score calculated by the model and common clinical features, univariate and multivariate analyses were carried out to assess whether the prognostic model could be used independently for prognostic prediction. In conclusion, the current study screened HCC prognostic gene signature based on public databases.
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Jones, Lauriann M., and Mustapha Mouloua. "A Student's Guide to HCI Research and Database Development." Proceedings of the Human Factors and Ergonomics Society Annual Meeting 49, no. 7 (September 2005): 774–77. http://dx.doi.org/10.1177/154193120504900707.
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This paper is intended to provide a useful guide and reference for those students (or researchers) attempting to familiarize themselves with the large body of HCI research available. This paper discusses trends, labs, funding sources, implications, and major contributions to HCI over the past decade (1995–2005) as documented through the British Journal of Behaviour & Information Technology. Several graphs are provided to illustrate patterns of interest and publication of HCI research with step-by-step guidance for the overwhelmed student (or researcher) for everything from narrowing relevant HCI journals and articles to a sampling of funding sources. All in the hope of providing a guide to understanding what has been done in the field, where to get started, and the direction HCI research may be going in the future.
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Doleh, Yunes, Huifen Wang, Ping Sun, Binbing Yu, and Iksha Herr. "Epidemiology and characteristics of patients (pts) with hepatocellular carcinoma (HCC) and care in the United States." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 231. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.231.
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231 Background: The incidence of liver and intrahepatic bile duct cancer, with HCC accounting for 72.7%, has doubled from 1992 to 2014 in the U.S. This study examined the latest epidemiology of HCC by analyzing 2 large U.S. databases. Methods: IBM MarketScan (IBM-MS) and Surveillance, Epidemiology, and End Results-National Program of Cancer Registries (SEER-NPCR) databases were analyzed separately. Pts (aged ≥ 18 years) with HCC as the primary cancer were identified from the IBM-MS database, who were covered by employer-provided commercial or Medicare Supplemental insurance. A new HCC diagnosis (Dx) was defined as the first HCC Dx using ICD-9/10 codes within the study period (Jan 2012-Sep 2017) and no other HCC Dx in the prior 12 months. Comorbidities, performance status, distribution of pts, and treatments received were described. In SEER-NPCR (Jan 2010-Dec 2014), a nationally representative patient sample was analyzed to describe the incidence and mortality of pts with HCC. Results: A total of 8,150 and 119,927 pts were identified in IBM-MS and SEER-NPCR, respectively. Pts were predominately male in both databases. The HCC incidence rates among the IBM-MS cohort were 5.9, 5.5, 4.9, and 4.7 per 100,000 person-years from 2013 to 2016, respectively. The downward trend in the HCC incidence rate post-2013 for this population coincided with the drop in HCC incidence rate from 2013 to 2014 in SEER-NPCR. Amongst the IBM-MS cohort, 6%, 36%, and 59% of pts had hepatitis B, hepatitis C, and cirrhosis at Dx, respectively. Most pts (88%) were considered having good performance status at Dx. Embolization and chemo/targeted therapies were the most common treatments received by pts irrespective of the disease stage (31% and 12%, respectively) and pts with de novo metastatic HCC (19% and 18%, respectively). About 44% of the HCC Dx occurred at hospital outpatient settings; 31% at inpatient settings and 23% at physician offices. Conclusions: This study identifies the recent epidemiologic changes in pts with HCC and characterizes their comorbidities in a commercially-insured and a U.S. representative population. These epidemiologic data may be important considerations for U.S. payers making coverage policies for pts with HCC.
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Glavaški, Mila, and Lazar Velicki. "Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach." Life 11, no. 8 (August 3, 2021): 785. http://dx.doi.org/10.3390/life11080785.
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Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a prevalence of 1 in 500 people and varying clinical presentations. Although there is much research on HCM, underlying molecular mechanisms are poorly understood, and research on the molecular mechanisms of its specific clinical presentations is scarce. Our aim was to explore the molecular mechanisms shared by HCM and its clinical presentations through the automated extraction of molecular mechanisms. Molecular mechanisms were congregated by a query of the INDRA database, which aggregates knowledge from pathway databases and combines it with molecular mechanisms extracted from abstracts and open-access full articles by multiple machine-reading systems. The molecular mechanisms were extracted from 230,072 articles on HCM and 19 HCM clinical presentations, and their intersections were found. Shared molecular mechanisms of HCM and its clinical presentations were represented as networks; the most important elements in the intersections’ networks were found, centrality scores for each element of each network calculated, networks with reduced level of noise generated, and cooperatively working elements detected in each intersection network. The identified shared molecular mechanisms represent possible mechanisms underlying different HCM clinical presentations. Applied methodology produced results consistent with the information in the scientific literature.
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Yan, Dong, Chunxiao Li, Yantong Zhou, Xue Yan, Weihua Zhi, Haili Qian, and Yue Han. "Exploration of Combinational Therapeutic Strategies for HCC Based on TCGA HCC Database." Oncologie 24, no. 1 (2022): 101–11. http://dx.doi.org/10.32604/oncologie.2022.020357.
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Brar, Gagandeep, Tim McNeel, Katherine McGlynn, Barry Graubard, Charalampos S. Floudas, M. Pia Morelli, Changqing Xie, Tim F. Greten, and Sean Altekruse. "Hepatocellular carcinoma (HCC) survival by etiology: A SEER-Medicare database analysis." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 201. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.201.
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201 Background: HCC is the 6thmost common occurring cancer worldwide and the 4th leading cause of cancer mortality, with a survival of 6-9 months. While survival varies by stage at diagnosis and treatment, the effect of HCC etiology on survival is unclear. We analyzed the SEER-Medicare database to evaluate whether HCC survival varied by etiology, after adjusting for stage, treatment, and survival. Methods: A total of 11,522 SEER-Medicare HCC cases (ICD-O-3 codes C22 for topography, 8170-8175 for morphology) met criteria for the Cox proportional hazard analyses to assess survival differences among the risk factors for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, alcohol disorders, and metabolic disorders. These analyses were adjusted for covariates for gender, age at diagnosis, race, ethnicity, tumor size and extent of disease, a modified Charlson Index of comorbidities, and treatments that included resection, transplantation, ablation, arterial directed therapy and radiotherapy. Cases with multiple and unknown etiologies were included in analyses, however genetic disorders and primary biliary cirrhosis were excluded due to their rarity. Results: HBV associated cases had the highest proportion of single nodules (40% vs 33% overall), localized stage disease (57% vs 49%), treatment (40% vs 27%), and greatest frequency of resection (18.6% vs 9%). Non-Hispanic Asians/Pacific Islanders accounted for 69% of HBV infection-related HCC cases but only 16% of all cases. HBV associated cases had better survival than did HCC cases with other etiologies. Specifically, after adjusting for demographic and clinical attributes, compared to cases with HBV infection, the risk of death was highest for alcohol-related HCC (HR=1.69; 95%CI:1.42-2.01) followed by multiple etiologies (HR = 1.40; 95% CI: 1.20-1.64), metabolic disorders (HR = 1.32; 95% CI: 1.13-1.55), HCV infection (HR = 1.30; 95% CI: 1.10-1.53), and HCC of unknown etiology (HR = 1.22; 95% CI: 1.04-1.43). Conclusions: Persons with HBV associated HCC had better survival than persons with HCC of other etiologies. Efforts to identify people with any etiologic risk factors for HCC, treat their conditions, and screen for HCC may improve overall survival.
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Zhang, Qin, Zhangying Feng, Mengxi Gao, and Liru Guo. "Determining novel candidate anti-hepatocellular carcinoma drugs using interaction networks and molecular docking between drug targets and natural compounds of SiNiSan." PeerJ 9 (February 16, 2021): e10745. http://dx.doi.org/10.7717/peerj.10745.
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Background SiNiSan (SNS) is an ancient traditional Chinese medicine (TCM) used to treat liver and spleen deficiencies. We studied the unique advantages of using SNS to treat hepatocellular carcinoma (HCC) with multiple components and targets to determine its potential mechanism of action. Methods The active compounds from the individual herbs in the SNS formula and their targets were mined from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). HCC-associated targets were collected from the TCGA and GEO databases and samples were collected from patients with stage III hepatocellular carcinoma. A compound-disease target network was constructed, visualized, and analyzed using Cytoscape software. We built a protein-protein interaction (PPI) network using the String database. We enriched and analyzed key targets using GSEA, GO, and KEGG in order to explore their functions. Autodock software was used to simulate the process of SNS molecules acting on HCC targets. Results A total of 113 candidate compounds were taken from SNS, and 64 of the same targets were chosen from HCC and SNS. The predominant targets genes were PTGS2, ESR1, CHEK1, CCNA2, NOS2 and AR; kaempferol and quercetin from SNS were the principal ingredients in HCC treatment. The compounds may work against HCC due to a cellular response to steroid hormones and histone phosphorylation. The P53 signaling pathway was significantly enriched in the gene set GSEA enrichment analysis and differential gene KEGG enrichment analysis. Conclusions Our results showed that the SNS component has a large number of stage III HCC targets. Among the targets, the sex hormone receptors, the AR and ESR1 genes, are the core targets of SNS component and the most active proteins in the PPI network. In addition, quercetin, which has the most targets, can act on the main targets (BAX, CDK1, CCNB1, SERPINE1, CHEK2, and IGFBP3) of the P53 pathway to treat HCC.
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Wei, Jialin, Zhiyuan Sun, Li Shi, Shaodan Hu, Da Liu, and Hong Wei. "Molecular Mechanism of Chrysin in Hepatocellular Carcinoma Treatment Based on Network Pharmacology and in Vitro Experiments." Natural Product Communications 16, no. 12 (December 2021): 1934578X2110672. http://dx.doi.org/10.1177/1934578x211067294.
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This study elucidated the potential molecular mechanism of chrysin in hepatocellular carcinoma (HCC) treatment using network pharmacology and in vitro experiments. Chrysin and candidate targets of HCC were obtained from the TCMSP and DrugBank databases, followed by mapping and screening of chrysin and HCC targets to identify the core targets of chrysin in HCC treatment. The interaction of chrysin and its targets, including CDK1, CDK5, as well as MMP9, were evaluated by molecular docking. The STRING database and Cytoscape (version 3.8.2) software were used to construct protein interactions and component-target networks of the core targets. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of the core target genes were performed using the DAVID database. Network pharmacology results showed that chrysin treatment of HCC was mainly related to cell proliferation and cell cycle. Accordingly, the cell counting kit-8 method and flow cytometry were used to detect the cell viability and cell cycle of hepatocarcinoma cells HCCLM3 and BEL-7402 in vitro. A total of 142 compound targets of chrysin, 12,179 HCC-related targets, and 116 intersecting targets were screened. The first 20 GO biological annotations of 17 core targets and the first 20 KEGG pathways mainly involved cell proliferation and cell cycle. In vitro experiments showed that chrysin inhibits the proliferation of human hepatocarcinoma cells (HCCLM3 and BEL-7402) in a dose-dependent manner. Moreover, chrysin induced cell cycle arrest in HCCLM3 and BEL-7402 cells in the G2 phase, and the expression was downregulated of cyclin-dependent kinases (CDKs), CDK2 and CDK4. Chrysin can offset HCC mainly by regulating the cell cycle and inhibiting cell proliferation. The network pharmacology results were verified, providing the basis for further study on the mechanism of chrysin intervention in HCC.
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Wang, Hang, Liang Yu, Yunfu Cui, and Jiaxin Huang. "G Protein Subunit Gamma 5 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma." Disease Markers 2022 (May 31, 2022): 1–14. http://dx.doi.org/10.1155/2022/1313359.
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Hepatocellular carcinoma (HCC) is one of the malignancies with an extremely inferior prognosis in the abdominal cavity, making it essential to develop more effective biomarkers for HCC. Although GNG5 has been linked to increased patient survival in a variety of human malignancies, no evidence has been found for its involvement in the development of HCC yet. Our study first analyzed the expression and prognosis of GNG5 in HCC using The Cancer Genome Atlas database (TCGA database) with the Gene Expression Omnibus database (GEO database) and found that GNG5 has a potential oncogenic role. Based on survival analysis, the clinical importance and prognostic value of the GNG5 gene were studied. Relying on tumor Immune Estimation Resource database (TIMER database), we analyzed the correlation between the GNG5 gene and HCC Immune infiltration cells. GNG5 expression levels were significantly higher in HCC tissues compared to normal liver tissues. HCC patients with high GNG5 expression had significantly reduced overall survival time and affected multiple immune cell infiltrates. Additionally, KEGG functional enrichment analysis indicated the PI3K-Akt signaling pathway as the most promising carcinogenic pathway associated with GNG5. This is the first comprehensive revelation of GNG5 as a possible new biological marker associated with immune infiltration in HCC. Additionally, it holds promise as an emerging target for HCC immunotherapy.
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Zhang, Shuqiao, Zhuomao Mo, Shijun Zhang, and Xinyu Li. "A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Artemisia annua on the Treatment of Hepatocellular Carcinoma." Evidence-Based Complementary and Alternative Medicine 2021 (February 22, 2021): 1–9. http://dx.doi.org/10.1155/2021/8947304.
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Objective. To investigate the potential active ingredients and underlying mechanisms of Artemisia annua (AA) on the treatment of hepatocellular carcinoma (HCC) based on network pharmacology. Methods. In the present study, we used a network pharmacological method to predict its underlying complex mechanism of treating HCC. First, we obtained relative compounds of AA based on the traditional Chinese medicine systems pharmacology (TCMSP) database and collected potential targets of these compounds by target fishing. Then, we built HCC-related targets target by the oncogenomic database of hepatocellular carcinoma (OncoDB.HCC) and biopharmacological network (PharmDB-K) database. Based on the matching results between AA potential targets and HCC targets, we built a protein-protein interaction (PPI) network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, the function annotation and signaling pathways of key targets were performed by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking. Results. A total of 19 main active ingredients of AA were screened as target prediction; then, 25 HCC-related common targets were seeked out via multiple HCC databases. The areas of nodes and corresponding degree values of EGFR, ESR1, CCND1, MYC, EGF, and PTGS2 were larger and could be easily found in the PPI network. Furthermore, GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis to accomplish the anti-HCC activity. The molecular docking analysis showed that quercetin could stably bind to the active pocket of EGFR protein 4RJ5 via LibDock. Conclusion. The anticancer effects of AA on HCC were predicted to be associated with regulating tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis via various pathways such as the EGFR signaling pathway, ESR1 signaling pathway, and CCND1 signaling pathway. It is suggested that AA might be developed as a broad-spectrum antitumor drug based on its characteristics of multicomponent, multipath, and multitarget.
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Sawyer, Peter, and John A. Mariani. "Database systems: challenges and opportunities for graphical HCI." Interacting with Computers 7, no. 3 (September 1995): 273–303. http://dx.doi.org/10.1016/0953-5438(95)93605-5.
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Hou, Liangjuan, Xin Zeng, Xuan Li, Chune Zhao, Juan Zou, Yukun Li, and Gang Liu. "MCM6 Promotes Hepatocellular Carcinoma Progression via the Notch Pathway: Clinical, Functional, and Genomic Insights." Computational and Mathematical Methods in Medicine 2022 (June 9, 2022): 1–21. http://dx.doi.org/10.1155/2022/3116303.
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Objective. To evaluate the expression profile of MCM6 in HCC and the relationship between MCM6 level and clinicopathological parameters through bioinformatics analysis of several databases. Methods. MCM expression level, clinical parameters, survival data, and gene set enrichment analysis were analyzed by bioinformatics database, including Oncomine™, UALCAN, HCCDB, TCGA, cBioPortal, and LinkedOmics. Real-time PCR, western blotting, and IHC staining were conducted to identify the expression of MCM6 in HCC compared to normal liver tissues. Results. Bioinformatics analysis indicated that the mRNA of MCM6 was obviously increased in multiple cancer types, especially in HCC. MCM6 level was positively associated with multiple clinical parameters (stage 3 and grades 3 and 4) and negatively associated with patient outcomes (overall survival). Moreover, enrichment of functions and signaling pathways analysis of MCM6 suggested that MCM6 might mediate DNA replication and cellular metabolism to promote the development and progression of HCC. Furthermore, IHC staining and western blotting indicated that the MCM6 was enhanced in HCC tissue, and MCM6 could promote HCC proliferation in activating Notch pathway via WB and bioinformatic analysis. Conclusion. This study actually revealed the expression and related functions of MCM6 in HCC. Furthermore, MCM6 is a carcinogenic role in activating Notch pathway to promote HCC cell proliferation, which may be a new prognostic biomarker and therapeutic target for HCC patients.
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Xiao, Jingchuan, and Yingai Zhang. "AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma." Evolutionary Bioinformatics 17 (January 2021): 117693432110575. http://dx.doi.org/10.1177/11769343211057589.
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The Aurora kinases form a family of 3 genes encoding serine/threonine kinases and are involved in the regulation of cell division during the mitosis. This study was designed to investigate the prognostic role of Aurora kinases in hepatocellular carcinoma (HCC). In this study, we analyzed the expression, overall survival (OS) data, promoter methylation level, and relationship with immunoinhibitors of Aurora kinases in patients with HCC from GEPIA2, UALCAN, OncoLnc, and TISIDB databases. Protein-protein interaction (PPI) network, gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analysis were performed using the STRING database and Cytoscape software. We found that the mRNA expression, stages of HCC, and OS of AURKA and AURKB in HCC tissues were significantly different from control tissues, but there were significant inconsistencies in promoter methylation level and relationship with immunoinhibitors for AURKA and AURKB. None of the above items were significantly different for AURKC. Furthermore, a hub module including AURKA, AURKB, and AURKC was identified within the PPI network constructed with the Molecular Complex Detection (MCODE) plug-in in Cytoscape software. Our results show that AURKB could be a potential biomarker for HCC prognosis.
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Liu, Bing, Zhicheng Dong, Yingzhi Lu, Jianhua Ma, Zhaoming Ma, and Hongwei Wang. "Prognostic Value of MUC16 Mutation and Its Correlation with Immunity in Hepatocellular Carcinoma Patients." Evidence-Based Complementary and Alternative Medicine 2022 (August 18, 2022): 1–9. http://dx.doi.org/10.1155/2022/3478861.
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Objective. Identifying gene mutation signatures will enable a better understanding for the occurrence, development, and prognosis of hepatocellular carcinoma (HCC) and provide some potential biomarkers for clinical practice. This study investigated the mutated genes in HCC patients and assessed their relationship with tumor mutation burden (TMB) and prognosis. Methods. The somatic mutation annotation format (MAF) document, mRNA expression matrix, and clinical information of HCC patients were obtained from the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA) database. The differences of TMB between the mutant type and the wild-type genes were detected using the Mann–Whitney U test. The link of gene mutations with prognosis was explored by the Kaplan–Meier analysis. The proportion of 22 immune cells’ composition was measured using CIBERSORT algorithm. Results. The two databases screened 16 common mutated genes, which included TP53, TTN, LRP1B, ZFHX4, MUC16, OBSCN, CSMD3, FLG, CSMD1, SYNE1, SPTA1, USH2A, KMT2C, PCLO, HMCN1, and FAT3. After a series of analysis, MUC16 mutation was found to be highly correlated with TMB and was regarded as an independent factor predicting HCC. Furthermore, gene set enrichment analysis (GSEA) indicated that the MUC16 mutation was significantly involved in HCC cell metabolism. Conclusions. MUC16 mutation seems to be a valuable potential biomarker for HCC development and its overall survival.
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Dang-Tan, Tam, Shiyuan Zhang, Ruben V. Tavares, Melissa Stutz, Afisi S. Ismaila, Julie Vaillancourt, Diane Corriveau, et al. "The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada." Canadian Respiratory Journal 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/8184915.
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Background. Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe). Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations). Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p<0.01) for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p<0.001). Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.
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Liu, Yang, Haoliang Zhang, Xue Han, and Xiaowei Xing. "Bioinformatics Methods Reveal the Biomarkers and the miRNA-mRNA Network in Hepatocellular Carcinoma." Journal of Healthcare Engineering 2022 (March 16, 2022): 1–8. http://dx.doi.org/10.1155/2022/9963096.
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Hepatocellular carcinoma (HCC) has threatened the health of humans, and few therapeutic strategies can completely uproot this illness. Bioinformatics methods have been widely used for investigating the pathological mechanisms of disease. In this study, datasets including GSE20077 and GSE108724, obtained from the Gene Expression Omnibus (GEO) database, were used for investigating the biomarker and molecular mechanism of HCC. The differentially expressed genes (DEGs) in the datasets were identified, and the targets of the miRNAs were searched in the miRDIP and miRNET databases. Enrichment analysis was performed for delving the molecular mechanism of DEGs, and protein-protein interaction (PPI) networks and miRNA-mRNA networks were used to reveal the hub nodes and the related interaction relationships. Moreover, the expression and diagnostic values of hub nodes were analyzed with the GEPIA2 database. The results showed that 53 upregulated miRNAs and 48 downregulated miRNAs were found in GSE20077, and 55 upregulated miRNAs and 69 downregulated miRNAs were found in GSE108724. Moreover, seven common miRNAs including miR-146b-5p, miR-338-3p, miR-375, miR-502-3p, miR-532-3p, miR-532-5p, and miR-557 were found in the datasets. The targets of the common miRNAs were related with the P53, HIF1, Wnt, and NF-κB pathways. Besides, YWHAZ and CDC42 were identified as the hub nodes and served as the downstream targets of miR-375-3p. The GEPIA2 database showed that YWHAZ and CDC42 were related with the survival rate of the patients. In conclusion, this study suggests that miR-375-3p functions as a tumor suppressor which could inhibit the progression of HCC via targeting YWHAZ and CDC42.
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Finkemeier, Christopher G., Chantal E. Holy, Jill W. Ruppenkamp, Mollie Vanderkarr, and C. Sparks. "Demographic and clinical profile of patients treated with proximal femoral nails – a 10-year analysis of more than 40,000 Cases." BMC Musculoskeletal Disorders 23, no. 1 (September 1, 2022). http://dx.doi.org/10.1186/s12891-022-05772-1.
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Abstract Background Hip fractures are common in elderly populations and can be life threatening. Changes in healthcare delivery and outcomes for patients with hip fracture treated with intramedullary nails are not well characterized. The objectives of our study were: 1) the characterization of patients treated with the Trochanteric Fixation Nail -Advanced™(TFNA) Proximal Femoral Nailing System or comparable nails (index) and estimate 12-month all-cause readmissions (ACR) and reoperations following index; and 2) the evaluation of 10-year healthcare utilization (HCU) trends for treatment of femoral fractures with femoral nails. Methods This is a retrospective database analysis using the Premier hospital database. All adults with femoral fracture treated with an intramedullary nail, from 2010 to Q3 2019, in the inpatient setting, were identified. Exclusion criteria included patients with bilateral hip surgery and presence of breakage at time of initial surgery. The primary outcome was ACR and reoperation, the secondary outcomes were healthcare utilization metrics. Variables included demographics, comorbidities (Elixhauser Index (EI)), surgical intervention variables and hospital characteristics. Results Forty-one thousand one hundred four patients were included in the study, of which 14,069 TFNA patients, with average age 77.9 (Standard deviation (SD): 12.0), more than 60% with 3 or more comorbidities (more than 64% for TFNA), 40% with severe or extreme disease severity and one third with severe or extreme risk for mortality. ACR reached 60.1% (95% confidence interval (CI): 59.6%-60.5%) – for TFNA: 60.0% (95%CI: 59.2%-60.8%). The reoperation rate was 4.0% (95%CI: 3.8%-4.2%) – for TFNA: 3.8% (95%CI: 3.5%-4.1%). Length of stay (LOS) averaged 5.8 days (SD: 4.8), and 12-month hip reoperation was 4.0% (3.8%-4.2%), in TFNA cohort: 3.8% (3.5%-4.1%). From 2010 to 2019: the percentage patients operated within 48 h of admission significantly increased, from 75.2% (95%CI: 74.3%-76.1%) to 84.3% (95%CI: 83.9%-84.6%); LOS significantly decreased, from 6.2 (95%CI: 6.0–6.4) to 5.6 (95%CI: 5.5–5.7) days; discharge to skilled nursing facilities (SNF) increased from 56.0% (95%CI: 54.8%-57.2%) to 61.5% (95%CI: 60.8%-62.2%); ACR rates decreased but reoperation rates remained constant. Conclusions ACR and reoperation rates were similar across device types and averaged 60.1% and 4.0%, respectively. Ten-year analyses showed reductions in hospital HCU and greater reliance on SNF.